Plasma renin activity (PRA), aldosterone excretion rate (AER) and an index of renal juxtaglomerular cell granulation (JGI) were determined in each of the 6 dogs at monthly intervals during, and 1, 2 and 4 months after the administration of spironolactone, 200 mg per day. PRA and JGI were significantly increased during spironolactone treatment and remained elevated above pretreatment values as long as 2 months after treatment was stopped. These data suggest that persistent past treatment effects of spironolactone should be considered when evaluating renin-aldosterone or renal histopathology in patients who have taken this drug.